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1.
  • Frisk, Jessica, et al. (författare)
  • Acupuncture improves health-related quality-of-life (HRQoL) and sleep in women with breast cancer and hot flushes
  • 2012
  • Ingår i: Supportive Care in Cancer. - : Springer. - 0941-4355 .- 1433-7339. ; 20:4, s. 715-724
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Evaluate effects of electro-acupuncture (EA) and hormone therapy (HT) on health-related quality-of-life (HRQoL) and sleep in breast cancer survivors with vasomotor symptoms. METHODS: Forty-five women, randomized to EA (n = 27) for 12 weeks or HT (n = 18) for 24 months, were followed for up to 2 years. Distress caused by, and numbers of, hot flushes, hours slept and times woken up/night, Psychological and General Well-being Index (PGWB) and Women's Health Questionnaire (WHQ) were registered before and during treatment and at 6, 9, 12, 18 and 24 months after start of treatment. RESULTS: After 12 weeks of EA (n = 19), WHQ improved from 0.32 (IQR 0.23-0.53) at baseline to 0.24 (IQR 0.12-0.39; p < 0.001) and PGWB from 78 (IQR 53-89) to 79 (IQR 68-93; p = 0.002). All sleep parameters improved and Hot Flush Score (HFS) decreased by 80%. At 12 months, WHQ, PGWB and all sleep parameters remained significantly improved (n = 14) and HFS decreased by 65%. After 12 weeks of HT (n = 18), WHQ improved from 0.29 (IQR 0.15-0.44) at baseline to 0.15 (IQR 0.05-0.22; p = 0.001), PGWB from 75 (IQR 59-88) to 90 (62-97; p = 0.102) and three of five sleep parameters improved. CONCLUSION: Both EA and HT increased HRQoL and sleep, probably through decreasing numbers of and distress by hot flushes. Although flushes decreased less in the EA group than in the HT group, HRQoL improved at least to the same extent maybe due to other effects of EA, not induced by HT, e.g. on anxiety, vitality and sleep, supported by subscale analyses. EA should be further evaluated as treatment for women with breast cancer and climacteric complaints, since HT no longer can be recommended for these women.
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2.
  • Furmark, Tomas, et al. (författare)
  • Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
  • 2005
  • Ingår i: Biol Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 58:2, s. 132-42
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • BACKGROUND: Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia. METHODS: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale. RESULTS: Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction. CONCLUSIONS: Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network.
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3.
  • Gladh, Mathias, 1971-, et al. (författare)
  • Prevalence of symptoms possibly related to PADAM, in a Swedish population aged 55, 65 and 75 years
  • 2005
  • Ingår i: Maturitas. - : Elsevier BV. - 0378-5122 .- 1873-4111. ; 50:3, s. 161-166
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: With age there is an average decline in the concentration of biologically active testosterone. It is still controversial if this leads to a clinically relevant deficit, "partial androgen deficiency of the ageing man" (PADAM). Our objective was to investigate the prevalence of a series of symptoms possibly associated with PADAM in an assumed normal-population of older men. Methods: We developed a questionnaire including items about symptoms possibly associated with PADAM as well as background data covering demography, medical history, mood status, medication, castration therapy, as well as smoking, exercise and alcohol habits. The 10 items of the ADAM-questionnaire, designed to predict low bio-available T, were also included. The questionnaire was sent to all 1885 men 55, 65 or 75-years-old, living in Linköping, Sweden. Results: We identified a number of symptoms that differed significantly (P<0.01) between age groups, e.g., "increased abdominal circumference", "decrease in muscle strength and/or endurance", "decreased libido", "less strong erection" and "lack of energy". From factorial analysis we found that the symptoms co-varied in four different groups. Conclusion: The prevalence of a number of symptoms differed significantly between age groups, but we cannot infer that there is a causal connection between an average age-dependent decline in testosterone function and these symptoms. There are several other ways to interpret these results like the existence of concurrent somatic and/or mood disorders or ageing as such. For this purpose further studies including measurements of testosterone concentrations relating to the findings of this study have to be performed. © 2004 Elsevier Ireland Ltd. All rights reserved.
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4.
  • Götmar, Anders, et al. (författare)
  • Symptoms in peri- and postmenopausal women in relation to testosterone concentrations. Data fromThe Women's Health in the Lund Area (WHILA) study
  • 2008
  • Ingår i: Climacteric. - : Informa UK Limited. - 1369-7137 .- 1473-0804. ; 11:4, s. 304-314
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of this study was to investigate possible associations between androgen concentrations in perimenopausal women and symptoms that may be associated with low androgen concentrations in the blood. Methods: All women born 1935 to 1945 living in a defined geographic area in Sweden (n=10766) were invited to a screening program that included physical and laboratory examinations and a questionnaire. Three groups were identified; premenopausal women, women on hormone replacement therapy (HRT) and postmenopausal women without HRT. Concentrations of testosterone (T), androstendione, Sex Hormone Binding Globulin and estradiol were measured. Waist Hip Ratio, Body Mass Index and Free Testosterone Index (FTI) were calculated. Results: 6908 women participated. The women on HRT had lower T and FTI and were less satisfied with mood and energy (p<0.05). Women with hot flushes had higher T and FTI and women reporting coldness had lower concentrations (p<0.05). Sexual well-being were not correlated to T or FTI (p>0.05). Conclusions: Lower T concentrations were associated with lower quality of life in perimenopausal women but not to sexual well-being. There must be other factors than decrements in sex hormones that contribute to the emergence of some perimenopausal symptoms.
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5.
  • Juran, Stephanie A, et al. (författare)
  • Unilateral Resection of the Anterior Medial Temporal Lobe Impairs Odor Identification and Valence Perception
  • 2015
  • Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The anterior medial temporal lobe (TL), including the amygdala, has been implicated in olfactory processing, e.g., coding for intensity and valence, and seems also involved in memory. With this background, the present study evaluated whether anterior medial TL-resections in TL epilepsy affected intensity and valence ratings, as well as free and cued identification of odors. These aspects of odor perception were assessed in 31 patients with unilateral anterior medial TL-resections (17 left, 14 right) and 16 healthy controls. Results suggest that the anterior medial TL is in particular necessary for free, but also cued, odor identification. TL resection was also found to impair odor valence, but not intensity ratings. Left resected patients rated nominally pleasant and unpleasant odors as more neutral suggesting a special role for the left anterior TL in coding for emotional saliency in response to odors.
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6.
  • Järvstråt, Lotta, et al. (författare)
  • Use of hormone therapy in Swedish women aged 80 years or older
  • 2015
  • Ingår i: Menopause. - 1072-3714 .- 1530-0374. ; 22:3, s. 275-278
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Menopausal symptoms such as hot flashes and night sweats may persist for 10 to 20 years or even longer. Information about the extent to which older women use hormone therapy is limited. The aim of this study was to determine the use of hormone therapy in Swedish women aged 80 years or older.Methods: The study is based on national register data on dispensed drug prescriptions (ie, prescribed therapy that has been provided to individuals by pharmacies) for hormone therapy and local low-dose estrogens.Results: Of 310,923 Swedish women who were aged at least 80 years, 609 (0.2%) were new users of hormone therapy. A total of 2,361 women (0.8%) were current users of hormone therapy. The median duration of hormone therapy use in new users was 257 days (25th to 75th percentiles, 611-120 d). About one in six women aged 80 years or older had used local vaginal estrogen therapy for at least four 3-month periods. The drugs were mainly prescribed by gynecologists and general practitioners.Conclusions: Our results show that a number of women aged 80 years or older still use hormone therapy and that most women who started a new treatment period had only one or two dispensations despite the median duration of treatment being more than half a year. Because at least some of the women aged 80 years or older who used hormone therapy probably did so owing to persistent climacteric symptoms, vasomotor symptoms and hormone therapy are still relevant issues that need to be discussed when counseling women around and after age 80.
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7.
  • Lindh-Åstrand, Lotta, et al. (författare)
  • Hormone therapy might be underutilized in women with early menopause.
  • 2015
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:4, s. 848-852
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY QUESTION Are Swedish women age 40–44 years with assumed early menopause ‘undertreated’ by hormone therapy (HT)?SUMMARY ANSWER Many women with probable early menopause discontinue their HT after a short period of time. Thus, they fail to complete the recommended replacement up to age 51–52 years, the average age of menopause.WHAT IS KNOWN ALREADY Spontaneous early menopause occurs in ∼5% of women age 40–45 years. Regardless of the cause, women who experience hormonal menopause due to bilateral oophorectomy before the median age of spontaneous menopause are at increased risk of cardiovascular disease, neurological disease, osteoporosis, psychiatric illness and even death.STUDY DESIGN, SIZE, DURATION The study is descriptive, and epidemiological and was based on the use of national registers of dispensed drug prescriptions (HT) linking registers from the National Board of Health and Welfare and Statistics Sweden from 1 July 2005 until 31 December 2011.PARTICIPANTS/MATERIALS, SETTING, METHODS The study population consisted of 310 404 women, 40–44 years old on 31 December 2005 who were followed from 1 July 2005 until 31 December 2011.MAIN RESULTS AND THE ROLE OF CHANCE Only 0.9% of women 40–44 years old started HT during the study period. A majority of these women used HT <1 year.LIMITATIONS, REASONS FOR CAUTION We do not know the indications that led to the prescription of HT but assume that early onset of menopause was the main reason. Because of the study design—making a retrospective study of registers—we can only speculate on the reasons for most of the women in this group discontinuing HT. Another limitation of this study is that we have a rather short observation time. However, we have up to now only been able to collect and combine the data since July 2005.WIDER IMPLICATIONS OF THE FINDINGS As the occurrence of spontaneous early menopause in women age 40–45 is reported to be ∼5%, the fact that <1% of Swedish women age 40–44 are prescribed HT, and can be shown also to have had the medication dispensed at a pharmacy suggests an unexpectedly low treatment rate. Some women with early menopause may have used combined contraceptives as supplementation therapy, but in Sweden HT is the recommended treatment for early menopause so any such women are not following this recommendation. Women who experience early menopause are at increased risk for overall morbidity and mortality, and can expect to benefit from HT until they have reached at least the median age of spontaneous menopause. It is therefore important to individualize the information given these women and to convey new knowledge in this area to gynaecologists and physicians in general as well as the recommendation that women in this group continue HT at least until the average age for spontaneous menopause is reached.
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8.
  • Lindh Åstrand, Lotta, et al. (författare)
  • Use of hormone therapy (HT) among Swedish women with contraindications - A pharmacoepidemiological cohort study
  • 2019
  • Ingår i: Maturitas. - : ELSEVIER IRELAND LTD. - 0378-5122 .- 1873-4111. ; 123, s. 55-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess how women in Sweden with breast cancer (BC), endometrial cancer (EC), and/or pulmonary embolism (PE) were dispensed menopausal hormone therapy (HT). Study design: A retrospective study of Swedish women aged 40 years or more on 31 December 2005 (n = 2,863,643), followed through to December 2011. The study analysed three mandatory national healthcare registries: the Swedish Prescribed Drug Register, the National Inpatient Register and the Cancer Register. New users were defined as having a first dispensation after at least a 9-month break, and thus were possible to identify from April 2006. New users with at least one of the diagnoses BC, EC or PE before the first dispensation were classified as having a relative or absolute contraindication for HT. Main outcome measures: The relative risks of having HT dispensed after being diagnosed with BC, EC and/or PE. Results: In total, 171,714 women had at least one of the diagnoses BC, EC or PE. The relative risk of having hormone therapy dispensed (current and new users) after being diagnosed with any of the diagnoses was significantly lower (PE, IRR 0.11, 95% CI 0.10-0.12;/ BC, IRR 0.12, 95% CI 0.11-0.13; EC, IRR 0.43, CI 0.40-0.46) than for women without these diagnoses. Conclusions: One in about 250 women started treatment with HT after being diagnosed with BC, PE or EC. Swedish prescribers seem to be well aware of the recommendations for HT use in women with contraindications. A few women, however, are prescribed HT despite having BC, EC or PE, possibly after careful evaluation of the risks and benefits and giving informed consent. Women with a history of PE were prescribed transdermal HT to a larger extent than women in general, in line with results from observational studies.
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9.
  • Ljunggren, Stefan, et al. (författare)
  • Alterations in high-density lipoprotein proteome and function associated with persistent organic pollutants
  • 2017
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 204-211
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a growing body of evidence that persistent organic pollutants (POPs) may increase the risk for cardiovascular disease (CVD), but the mechanisms remain unclear. High- density lipoprotein (HDL) acts protective against CVD by different processes, andwe have earlier found that HDL from subjects with CVD contains higher levels of POPs than healthy controls. In the present study, we have expanded analyses on the same individuals living in a contaminated community and investigated the relationship between the HDL POP levels and protein composition/ function. HDL from17 subjectswas isolated by ultracentrifugation. HDL protein composition, using nanoliquid chromatography tandemmass spectrometry, and antioxidant activity were analyzed. The associations of 16 POPs, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, with HDL proteins/functionswere investigated by partial least square and multiple linear regression analysis. Proteomic analyses identified 118 HDL proteins, of which ten were significantly (p b 0.05) and positively associated with the combined level of POPs or with highly chlorinated PCB congeners. Among these, cholesteryl ester transfer protein and phospholipid transfer protein, as well as the inflammatory marker serum amyloid A, were found. The serum paraoxonase/arylesterase 1 activity was inversely associated with POPs. Pathway analysis demonstrated that up- regulated proteinswere associatedwith biological processes involving lipoproteinmetabolism, while down- regulated proteinswere associatedwith processes such as negative regulation of proteinases, acute phase response, platelet degranulation, and complement activation. These results indicate an association between POP levels, especially highly chlorinated PCBs, and HDL protein alterations that may result in a less functional particle. Further studies are needed to determine causality and the importance of other environmental factors. Nevertheless, this study provides a first insight into a possible link between exposure to POPs and risk of CVD.
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10.
  • Nilsonne, Gustav, et al. (författare)
  • Learning in a simple biological system : a pilot study of classical conditioning of human macrophages in vitro
  • 2011
  • Ingår i: Behavioral and Brain Functions. - : Springer Science and Business Media LLC. - 1744-9081. ; 7, s. 47-
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation. However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions.
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12.
  • Risto, Olof, et al. (författare)
  • Elderly men with a history of distal radius fracture have significantly lower calcaneal bone density and free androgen index than age-matched controls
  • 2012
  • Ingår i: The Aging Male. - : Informa Healthcare. - 1368-5538 .- 1473-0790. ; 15:1, s. 59-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Age related bone loss is widely accepted as related to decreased serum levels of circulating sex hormones. Epidemiological data also show distal radius fractures in men to be a sensitive marker of bone fragility. The aim of this study was to assess if men with a history of distal radius fracture have lower bone mass density (BMD), lower free androgen index (FAI), lower total testosterone (T) and lower bio-available testosterone (Bio-T) than healthy age-matched controls. Patients and methods: A case-control study is based on consecutive cases treated for low energy distal radius fracture at our department and age-matched controls. Thirty-nine men treated between 1997-2004 and 45 age-matched controls underwent calcaneal bone density measurements (t-score) and analyses of T, Bio-T and serum hormone binding globulin (SHBG). Results: The fracture group had lower BMD (p andlt; 0.01) and lower FAI (p = 0.01). Linear regression analysis showed a correlation between Bio-T and t-scores (p = 0.03). Using analysis of covariance, a significant difference with lower Bio-T in the fracture group was shown. Conclusion: Bio-T seems to correlate with BMD in elderly men and may serve as a marker for increased fracture risk in this patient group.
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13.
  • Spetz, Anna-Clara, et al. (författare)
  • Change in testosterone concentrations over time is a better predictor than the actual concentrations for symptoms of late onset hypogonadism
  • 2011
  • Ingår i: The Aging Male. - : Informa Healthcare. - 1368-5538 .- 1473-0790. ; 14:4, s. 249-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Symptoms of late-onset hypogonadism (LOH) and concentrations of testosterone (T) and bioavailable testosterone (BT) were studied in relation to the data from the same men 5 years earlier. less thanbrgreater than less thanbrgreater thanMethods. In 2008, 282 men, aged 60-82 years, answered a questionnaire regarding demographic data, medical history, different symptoms of LOH and the 10 questions from the Androgen Decline in Aging Males (ADAM)-questionnaire. Blood samples were analysed for concentrations of T and calculations were made for BT. less thanbrgreater than less thanbrgreater thanResults. A total of 87.2% of the questionnaires were returned and analysed, and 75.2% of the responders gave blood samples. The oldest third of the men were most affected by LOH symptoms (p andlt; 0.05). Both T and BT concentrations decreased during the 5 years (p andlt; 0.05) but only the symptom less strong erections changed significantly (p andlt; 0.05). Men reporting one of the four specific symptoms from the ADAM-questionnaire for the first time in 2008 had a higher loss of T and BT than men who had unchanged or fewer symptoms than that reported in 2003. less thanbrgreater than less thanbrgreater thanConclusions. The magnitude of the decrease in concentrations is a better predictor of LOH than are the actual concentrations of T and BT. A combination of symptoms predicts LOH better than any single symptom.
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14.
  • Spetz, Anna-Clara, 1973-, et al. (författare)
  • Hot flushes in a male population aged 55, 65, and 75 years, living in the community of Linköping, Sweden
  • 2003
  • Ingår i: Menopause. - : Ovid Technologies (Wolters Kluwer Health). - 1072-3714 .- 1530-0374. ; 10:1, s. 81-87
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:Hot flushes are as common in castrated men as in menopausal women. We investigated whether hot flushes exist in a normal aging male population and to what extent.DESIGN:A questionnaire was sent to all men living in Linköping, Sweden, who were 55, 65, and 75 years old ( = 1,885). The questionnaire asked for demographic data, medical history, mood status, medication, castrational therapy, and smoking, exercise, and alcohol habits, among other items. We asked specifically for current hot flushes unrelated to exercise or a warm environment.RESULTS:Of the questionnaires received, 1,381 were eligible for evaluation; 33 were analyzed separately because these men had been castrated. Hot flushes of any frequency were reported by 33.1% of noncastrated men, 4.3% reported flushes at least a few times per week, and 1.3% reported daily flushes. Half of the men reporting flushes were also bothered by them, ie, almost every sixth man in total. We found a relation between occurrence of hot flushes and other symptoms thought to be related to low testosterone concentration, such as decreased muscle strength or endurance, decreased enjoyment of life, sadness or grumpiness, and lack of energy ( < 0.05).CONCLUSIONS:Hot flushes occur in one third of a population of noncastrated older men, approximately half of whom consider flushes as bothersome. Neither the mechanisms nor whether the symptoms would respond to testosterone supplementation is known. Androgen substitution to treat symptoms possibly related to a male climacteric is still controversial. Studies are needed to evaluate the needs for and the effects of androgen treatment on vasomotor symptoms.
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15.
  • Spetz, Anna-Clara, et al. (författare)
  • Symptoms of testosterone deficiency in early middle aged men
  • 2012
  • Ingår i: The Aging Male. - : Informa Healthcare. - 1368-5538 .- 1473-0790. ; 15:2, s. 78-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Symptoms of testosterone deficiency and concentrations of testosterone (T) and bioavailable testosterone (BT) were studied in 35-and 45-year-old men. Methods: A questionnaire, was sent to all 35-and 45-year-old men in Linkoping, Sweden (n = 1998). The questionnaire has earlier been used for 55- to 75-year-old men and included demographic data, medical history, different symptoms possibly of T deficiency and the 10 questions from the "ADAM-questionnaire". Totally 200 men randomly selected among the men who answered the questionnaire were asked to give blood samples for analysis of T-and BT-concentrations. Results: A total of 38.7% of the questionnaires were returned and analysed, and 43.5% of the 200 randomly selected men gave blood samples. The older age group reported more symptoms that may be connected to low B and BT and had lower T-and BT-concentrations. Less strong erections and higher alcohol consumption were associated with lower concentrations of BT in 45-year-old men. Conclusions: The burden of symptoms possibly related to low T concentrations were higher in 45-year-old men, and BT and T were lower. However, due to the low answer frequency and number of blood samples analyzed no general conclusions can be drawn.
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16.
  • Sundell, Micaela, et al. (författare)
  • Pulmonary embolism in menopausal hormone therapy : a population-based register study
  • 2022
  • Ingår i: Climacteric. - : Taylor & Francis. - 1369-7137 .- 1473-0804. ; 25:6, s. 615-621
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration.METHOD: The population-based case-control study covered 1,771,253 women aged 40-69 years, during 2006-2015. Diagnoses of PE (n = 13,974) and drug dispensations were received from national validated registers.RESULTS: Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23-3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate.DISCUSSION: The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect.CONCLUSION: PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.
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17.
  • Willander, Kerstin, et al. (författare)
  • MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemia
  • 2010
  • Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 85:3, s. 251-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. Objective: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). Patients: A total of 210 patients with B-CLL were followed for up to 19 yr. Results: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. Conclusion: In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients.
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18.
  • Willander, Kerstin, et al. (författare)
  • NOTCH1 mutations influence survival in chronic lymphocytic leukemia patients
  • 2013
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: NOTCH1 PEST domain mutations in chronic lymphocytic leukemia have recently been shown to be of prognostic relevance. Both NOTCH1 and NOTCH2 are constitutively activated in B-cell CLL but not expressed in normal B cells and may be involved in survival and resistance to apoptosis in CLL. We screened for mutations in different parts of both NOTCH1 and NOTCH2 genes and related the changes to survival and other known risk factors. Methods: In a cohort of 209 CLL patients, we used single strand conformation analysis to determine which of the samples carrying the NOTCH mutations and direct dideoxy sequencing was used to determine the exact nucleotide changes. Kaplan-Meier curves and log rank test were used to determine overall survival for NOTCH1 mutated cases and Cox regression analysis was used to calculate hazardous ratios. Results: In the present study, we found NOTCH1 PEST domain mutations in 6.7% of the cases. A shorter overall survival was found in patients with NOTCH1 mutations compared to wildtype (p = 0.049). Further, we also examined the extracellular and the heterodimerisation domains of the NOTCH1 gene and the PEST domain and heterodimerisation domain of the NOTCH2 gene, but no mutations were found in these regions. NOTCH1 mutations were most commonly observed in patients with unmutated IGHV gene (10/14), and associated with a more aggressive disease course. In addition, NOTCH1 mutations were almost mutually exclusive with TP53 mutations. In the combined group of NOTCH1 (6.7%) or TP53 (6.2%) mutations, a significant difference in overall survival compared to the wildtype NOTCH1 and TP53 was found (p = 0.002). Conclusions: Both NOTCH1 and TP53 mutations seem to be independent predictive markers for worse outcome in CLL-patients and this study emphasizes the contention that NOTCH1 mutations is a novel risk marker.
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20.
  • Ågren, Thomas, et al. (författare)
  • Effective Connectivity of Fear Circuitry and Emotion Regulation in Specific Phobia
  • 2011
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The aim of the present study was to characterize effective brain connectivity patterns in patients with specific phobia. Methods: Sixteen patients with specific phobia were exposed to phobic and fear-relevant but non-phobic stimuli while regional cerebral blood flow was measured using [15O]-labelled water and positron emission tomography. Self reported state anxiety was also evaluated using the Spielberger State Anxiety Inventory (STAI-S). Different connectivity architectures were built based on five regions of interest (ROIs): the amygdala; subgenual anterior cingulate cortex (sACC) area 25; anterior midcingulate cortex (aMCC) area 24; insular cortex and dorsolateral prefrontal cortex (DLPFC) area 8. The ROIs were chosen based on their role in generating and attenuating fear. Structural equations modelling and Bayesian inference were used to assign probabilities to all possible architectures. Results: Top ranking models reveal different connectivity patterns resulting from phobic and non-phobic exposure. When exposed to phobic stimuli sACC appear to be driving the network. In contrast, when exposed to non-phobic stimuli the DLPFC is more active and dampen amygdala activity. This could reflect successful reappraisal processes during non-phobic exposure. The DLPFC correlated negatively (r=-0.49) with STAI-S during non-phobic exposure, but not phobic exposure also suggesting that emotional regulation fails in phobia. No direct correlation between amygdala activity and STAI-S was evident during either phobic or non-phobic conditions. Conclusions: These results suggest that emotional control processes operative when exposed to fear-relevant, but non-phobic cues are impaired during exposure to phobic stimuli.
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21.
  • Aarnio, Mikko, et al. (författare)
  • Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The understanding of etiological mechanisms of whiplash associated disorder is still inadequate. Objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in whiplash associated disorder would facilitate diagnosis, strengthen patients’ subjective pain reports and aid clinical decisions eventually leading to better treatments. In the current study, we further evaluated the potential to use [11C]D-deprenyl PET/CT to visualize inflammation after whiplash injury. Sixteen patients with whiplash injury grade II were recruited at the emergency department and underwent [11C]D-deprenyl PET/CT in the acute phase and at 6 months after injury. Subjective pain levels, self rated neck disability and active cervical range of motion were recorded at each imaging session. Results showed that the molecular aspects of inflammation and possible tissue injuries after acute whiplash injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. An altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self rated disability during both imaging occasions. These findings may contribute to a better understanding of affected peripheral structures in whiplash injury and strengthens the idea that PET/CT detectable organic lesions in peripheral tissue may be relevant for the development of persistent pain and disability in whiplash injury.Perspective: This article presents a novel way of objectively visualizing possible structural damage and inflammation that cause pain and disability in whiplash injury. This PET method can bring an advance in pain research and eventually would facilitate the clinical management of patients in pain.
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22.
  • Aarnio, Mikko, et al. (författare)
  • Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography
  • 2022
  • Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 163:3, s. 489-495
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.
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23.
  • Abate Waktola, Ebba Abate, et al. (författare)
  • Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia
  • 2019
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.
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24.
  • Abdelrahman, Islam, et al. (författare)
  • Division of overall duration of stay into operative stay and postoperative stay improves the overall estimate as a measure of quality of outcome in burn care.
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients and Methods: Surgically managed burn patients admitted between 2010-14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay.less thanbr /greater thanResults: Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, pless than0.01). The size of the burn, and the number of operations, were the independent factors that influenced operative stay (R2 0.65). Except for the size of the burn other factors were associated with duration of postoperative stay: wound related, psychological and other medical causes, advanced medical support, and accommodation arrangements before discharge, of which the two last were the most important with an increase of (mean) 12 and 17 days (pless than0.001, R2 0.51).less thanbr /greater thanConclusion: Adjusted operative stay showed less variation than total hospital stay and thus can be considered a more accurate outcome measure for surgically managed burns. The size of burn and number of operations are the factors affecting this outcome measure.
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25.
  • Abdelrahman, Islam, et al. (författare)
  • Improvement in mortality at a National Burn Centre since 2000 : Was it the result of increased resources?
  • 2017
  • Ingår i: Medicine. - : Wolters Kluwer. - 0025-7974 .- 1536-5964. ; 96:25
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract The aim of this study was to find out whether the charging costs (calculated using interventional burn score) increased as mortality decreased. During the last 2 decades, mortality has declined significantly in the Linköping Burn Centre. The burn score that we use has been validated as a measure of workload and is used to calculate the charging costs of each burned patient. We compared the charging costs and mortality in 2 time periods (2000–2007 and 2008–2015). A total of 1363 admissions were included. We investigated the change in the burn score, as a surrogate for total costs per patient. Multivariable regression was used to analyze risk-adjusted mortality and burn score. The median total body surface area % (TBSA%) was 6.5% (10–90 centile 1.0–31.0), age 33 years (1.3–72.2), duration of stay/ TBSA% was 1.4 days (0.3–5.3), and 960 (70%) were males. Crude mortality declined from 7.5% in 2000–2007 to 3.4% in 2008–2015, whereas the cumulative burn score was not increased (P=.08). Regression analysis showed that risk-adjusted mortality decreased (odds ratio 0.42, P=.02), whereas the adjusted burn score did not change (P=.14, model R2 0.86). Mortality decreased but there was no increase in the daily use of resources as measured by the interventional burn score. The data suggest that the improvements in quality obtained have been achieved within present routines for care of patients (multidisciplinary/ orientated to patients’ safety).Abbreviation: TBSA% = total body surface area %.
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26.
  • Abdelrahman, Islam, 1982-, et al. (författare)
  • Use of the burn intervention score to calculate the charges of the care of burns
  • 2019
  • Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 45:2, s. 303-309
  • Tidskriftsartikel (refereegranskat)abstract
    • Background To our knowledge this is the first published estimate of the charges of the care of burns in Sweden. The Linköping Burn Interventional Score has been used to calculate the charges for each burned patient since 1993. The treatment of burns is versatile, and depends on the depth and extension of the burn. This requires a flexible system to detect the actual differences in the care provided. We aimed to describe the model of burn care that we used to calculate the charges incurred during the acute phase until discharge, so it could be reproduced and applied in other burn centres, which would facilitate a future objective comparison of the expenses in burn care. Methods All patients admitted with burns during the period 2010–15 were included. We analysed clinical and economic data from the daily burn scores during the acute phase of the burn until discharge from the burn centre. Results Total median charge/patient was US$ 28 199 (10th–90th centiles 4668-197 781) for 696 patients admitted. Burns caused by hot objects and electricity resulted in the highest charges/TBSA%, while charges/day were similar for the different causes of injury. Flame burns resulted in the highest mean charges/admission, probably because they had the longest duration of stay. Mean charges/patient increased in a linear fashion among the different age groups. Conclusion Our intervention-based estimate of charges has proved to be a valid tool that is sensitive to the procedures that drive the costs of the care of burns such as large TBSA%, intensive care, and operations. The burn score system could be reproduced easily in other burn centres worldwide and facilitate the comparison regardless of the differences in the currency and the economic circumstances.
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27.
  • Abdelrahman, Islam, 1982-, et al. (författare)
  • Validation of the burn intervention score in a National Burn Centre
  • 2018
  • Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; :5, s. 1159-1166
  • Tidskriftsartikel (refereegranskat)abstract
    • The Linköping burn score has been used for two decades to calculate the cost to the hospital of each burned patient. Our aim was to validate the Burn Score in a dedicated Burn Centre by analysing the associations with burn-specific factors: percentage of total body surface area burned (TBSA%), cause of injury, patients referred from other (non-specialist) centres, and survival, to find out which of these factors resulted in higher scores. Our second aim was to analyse the variation in scores of each category of care (surveillance, respiration, circulation, wound care, mobilisation, laboratory tests, infusions, and operation).We made a retrospective analysis of all burned patients admitted during the period 2000–15. Multivariable regression models were used to analyse predictive factors for an increased daily burn score, the cumulative burn score (the sum of the daily burn scores for each patient) and the total burn score (total sum of burn scores for the whole group throughout the study period) in addition to sub-analysis of the different categories of care that make up the burn score.We retrieved 22 301 daily recordings for inpatients. Mobilisation and care of the wound accounted for more than half of the total burn score during the study. Increased TBSA% and age over 45 years were associated with increased cumulative (model R2 0.43, p < 0.001) and daily (model R2 0.61, p < 0.001) burn scores. Patients who died had higher daily burn scores, while the cumulative burn score decreased with shorter duration of hospital stay (p < 0.001).To our knowledge this is the first long term analysis and validation of a system for scoring burn interventions in patients with burns that explores its association with the factors important for outcome. Calculations of costs are based on the score, and it provides an indicator of the nurses’ workload. It also gives important information about the different dimensions of the care provided from thorough investigation of the scores for each category.
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28.
  • Abrahamsson, Thomas R, et al. (författare)
  • Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
  • 2009
  • Ingår i: Journal of pediatric gastroenterology and nutrition. - : Lippincott Williams & Wilkins. - 1536-4801 .- 0277-2116. ; 49:3, s. 349-354
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization. MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods. RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization. CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.
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29.
  • Abrahamsson, Thomas R, 1968-, et al. (författare)
  • Probiotics in prevention of IgE-associated eczema : a double-blind, randomized, placebo-controlled trial
  • 2007
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 119:5, s. 1174-1180
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri. METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected. CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.
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30.
  • Ahmadpour, Doryaneh, 1973, et al. (författare)
  • Inventory study of an early pandemic COVID- 19 cohort in South-Eastern Sweden, focusing on neurological manifestations
  • 2023
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 18:1 January
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Neurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection. The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county ofÖstergötland in southeastern Sweden. Methods This is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. Results Seventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. Conclusion Neurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.
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31.
  • Ahs, Fredrik, et al. (författare)
  • High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia
  • 2009
  • Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 47:3, s. 815-820
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying brain systems that regulate or modulate autonomic nervous system functions may identify pathways through which psychosocial factors can influence health and disease. Reduced high-frequency heart rate variability (HF-HRV) characterizes anxiety disordered patients and is predictive of adverse myocardial events. Sex differences in the prevalence of anxiety disorders and cardiac diseases implicate the possibility of sex specific neural regulation of HF-HRV. We investigated the correlation between HF-HRV and regional cerebral blood flow (rCBF) in 28 subjects (15 women) with social phobia undergoing a stressful public speaking task. Regional CBF was measured with [(15)O] water positron emission tomography. Stress induced rCBF correlated positively with HF-HRV in the right supra genual anterior cingulate cortex Brodmann's area (BA) 32, the right head of the caudate nucleus and bilaterally in the medial prefrontal cortex (BA10), extending into the dorsolateral prefrontal cortex (BA46) in the left hemisphere. Men showed larger positive co-variation in the caudate than women. These findings underscore the importance of the emotional division of the anterior cingulate cortex, the prefrontal cortex and the striatum in cardiovagal activity. The study replicates and extends results from published functional neuroimaging studies on cardioregulatory or modulatory areas in healthy subjects to men and women with social phobia. Moreover, caudate functions, possibly related to dopaminergic neurotransmission, have sexually dimorphic effects on vagal modulation of the heart.
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32.
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33.
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34.
  • Alfredsson, Joakim, et al. (författare)
  • Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes
  • 2014
  • Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 168:4, s. 522-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.
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35.
  • Andersson, Gerhard, 1966-, et al. (författare)
  • Consequences of suppressing thoughts about tinnitus and the effects of cognitive distraction on brain activity in tinnitus patients
  • 2006
  • Ingår i: Audiology & neuro-otology. - : S. Karger AG. - 1420-3030 .- 1421-9700. ; 11:5, s. 301-309
  • Tidskriftsartikel (refereegranskat)abstract
    • Tinnitus is the perception of sound in the absence of any appropriate external stimulus. Based on the clinical observation that tinnitus patients may distract themselves from their sounds, we performed an experimental test on the effects of suppressing thoughts about tinnitus with 45 tinnitus patients, to systematically evaluate the immediate consequences of suppressing thought vs. attending to tinnitus. Suppression instructions tended to lead to a subsequent decrease in tinnitus-related thoughts, whereas attention to tinnitus resulted in an increase in such thoughts. No effects were seen in a control group who neither suppressed nor attended to their tinnitus. In an independent positron emission tomography study of cerebral blood flow with 8 patients we found that silent backward counting ('serial sevens test') led to a decrease in neural activity in auditory cortex, as well as perceived decrease of tinnitus loudness and annoyance. Thus, distraction that altered the tinnitus experience seemed to attenuate auditory cortex activity.
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36.
  • Andersson, Maria, et al. (författare)
  • Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting
  • 2019
  • Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : SPRINGER. - 0934-9723 .- 1435-4373. ; 38:7, s. 1223-1234
  • Tidskriftsartikel (refereegranskat)abstract
    • Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012-2013. The criterion early appropriate antibiotic treatment was defined as administration of the first dose of adequate antibiotics within 1h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.
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37.
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38.
  • Annas, Peter, et al. (författare)
  • Genetic influences on classical-conditioning
  • 1995
  • Ingår i: PSYCHOPHYSIOLOGY. - : SOC PSYCHOPHYSIOL RES. - 0048-5772. ; 32, s. S16, Suppl 1-, s. 16-
  • Tidskriftsartikel (refereegranskat)
  •  
39.
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40.
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41.
  • Appel, Lieuwe, et al. (författare)
  • Altered NK1-receptor availability in patients with post traumatic stress disorder
  • 2009
  • Ingår i: [Biological Psychiatry 2009, 65(8), Suppl. 1, 118S, no. 394]. - : Elsevier BV. ; , s. 118S-
  • Konferensbidrag (refereegranskat)abstract
    • Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after one or more traumatic events causing extreme stress or grave physical harm. The neurokinin-1 (NK1) receptor is the primary receptor for substance P (SP); a neuropeptide suggested being involved in anxiety and depression. The present study investigated differences in NK1-receptor availability between PTSD patients and healthy controls, using positron emission tomography (PET). Methods: Eleven male refugee patients (age: 41±10) with DSM-IV defined PTSD and nine healthy male control subjects (age: 33±10) were investigated using the PET-tracer [11C]GR205171, supplied by Uppsala Imanet. GR205171 is a highly selective NK1-receptor antagonist. Scans were performed during 60 minutes in the resting state. Parametric images were generated using the graphical reference Patlak method assuming irreversible binding of [11C]GR205171 from 20-60 minutes and having cerebellum as reference region. Exploratory whole brain analyses were performed using the statistical parametric mapping (SPM2) software. Results: PTSD patients had lower [11C]GR205171 binding compared to controls, in frontal cortical clusters encompassing bilaterally insula and left Brodmann area 11, reflecting lower NK1-receptor availability. No areas were found in which PTSD patients had higher [11C]GR205171 binding. Conclusions: This is the first study reporting differences in NK1-receptor availability in PTSD patients relative to controls. A tentative conclusion is that PTSD patients have a down regulation of the NK1-receptor system, which could be either a risk factor or due to emotional trauma processing.
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42.
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43.
  • Arnqvist, Hans, et al. (författare)
  • Impact of HbA(1c) Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study
  • 2022
  • Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 45:11, s. 2675-2682
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To evaluate HbA(1c) followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA(1c) (wHbA(1c)) was calculated by integrating the area under all HbA(1c) values. Complications were analyzed in relation to wHbA(1c) categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA(1c) did not develop PDR or macroalbuminuria. The lowest wHbA(1c) values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA(1c), being 74% and 44% in the highest category, wHbA(1c) >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA(1c) values. CONCLUSIONS wHbA(1c) followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA(1c) <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.
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44.
  • Axelson, Olav, 1937-, et al. (författare)
  • Assessing dose-response relationships by cumulative exposures in epidemiological studies
  • 2007
  • Ingår i: American Journal of Industrial Medicine. - : Wiley. - 0271-3586 .- 1097-0274. ; 50:3, s. 217-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: If the occurrence of disease monotonically increases with the degree of exposure in an epidemiologic study, a dose-response (or exposure-response) relationship is indicated and facilitates the interpretation that the exposure has a causal role. It is not uncommon, however, that there is some effect in terms of an overall increased relative risk but no clear dose-response relationship. Methods: Models presented here show that cumulative exposure, as involving the duration of exposure, is not an adequate parameter when more recent exposure or the intensity of the exposure plays the greater role for the disease outcome. Conclusions: In lack of a dose-response pattern by cumulative exposure, the interpretation of an overall increased risk might well be that there is no definite effect. The proper consideration should be, however, that the measure of exposure could be inadequate, suggesting a need for further analyses and evaluations of the material studied. © 2007 Wiley-Liss, Inc.
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45.
  • Axelson, Olav, 1937-, et al. (författare)
  • Leukemia in childhood and adolescence and exposure to ionizing radiation in homes built from uranium-containing alum shale concrete
  • 2002
  • Ingår i: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983 .- 1531-5487. ; 13:2, s. 146-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Concerns in Sweden about indoor radon around 1980 prompted measurements of gamma-radiation from the facades of houses to identify those constructed of uranium-containing alum shale concrete, with potentially high radon concentrations. To evaluate any possible risk of acute lymphocytic leukemia from exposure to elevated gamma-radiation in these homes, we identified the acute lymphocytic leukemia cases less than 20 years of age in Sweden during 1980-1989 as well as eight controls per case from the population registry, matching on age, gender, and county. Using the existing measurements, exposure was assessable for 312 cases and 1,418 controls from 151 properly measured municipalities. A conditional logistic odds ratio of 1.4 (95% confidence interval = 1.0-1.9) was obtained for those ever having lived in alum shale concrete houses, with the average exposure exceeding 0.10 microsieverts per hour. Comparing those who ever lived in alum shale concrete houses (divided by higher and lower annual average exposure) with those who never lived in such houses, we found a weak dose-response relation. The results suggest some risk of acute lymphocytic leukemia from indoor ionizing radiation among children and young adults.
  •  
46.
  • Backstrom, D., et al. (författare)
  • Letter: Outcome of trauma patients
  • 2010
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Blackwell Publishing Ltd. - 0001-5172 .- 1399-6576. ; 54:7, s. 902-903
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • n/a
  •  
47.
  • Baldwin, David S, et al. (författare)
  • Manifesto for a European anxiety disorders research network.
  • 2010
  • Ingår i: European neuropsychopharmacology. - : Elsevier BV. - 1873-7862 .- 0924-977X. ; 20:6, s. 426-432
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the size, burden and costs of anxiety disorders, many patients remain unrecognised, and the effectiveness of evidence-based interventions in routine clinical practice can be disappointing. The European College of Neuropsychopharmacology (ECNP) has established the ECNP Network Initiative (ECNP-NI) to help meet the goal of extending current understanding of the causes of central nervous system disorders, thereby contributing to improvements in clinical outcomes and reducing the associated societal burden. The Anxiety Disorders Research Network (ADRN) has been adopted within the ECNP-NI: this consensus statement summarises its overall aims and objectives.
  •  
48.
  • Bas-Hoogendam, Janna Marie, et al. (författare)
  • Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
  • 2017
  • Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
  •  
49.
  •  
50.
  • Bergman, Olle, 1978, et al. (författare)
  • Association between amygdala reactivity and a dopamine transporter gene polymorphism.
  • 2014
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.
  •  
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